• Crohn disease
• Inflammatory bowel disease
• Non-alcoholic fatty liver disease
• Ulcerative colitis

• Crohn’s disease
• inflammatory bowel diseases
• liver steatosis
• ulcerative colitis

• Humans
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/pathology
• Quality of Life
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/epidemiology
• Inflammatory Bowel Diseases/diagnosis
• Crohn Disease
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/epidemiology

• body mass index
• fat mass
• fat-free mass
• fatty liver
• ulcerative colitis

• Crohn’s disease
• fatty liver
• inflammatory bowel disease
• ulcerative colitis

• 111-CCH-IRP-011 and 112-CCH-IRP-033 Changhua Christian Hospital

• Crohn’s disease
• biologic therapy
• inflammatory bowel diseases
• liver toxicity
• small molecules
• ulcerative colitis

• Humans
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/epidemiology
• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/drug therapy
• Hepatitis, Autoimmune/complications
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/drug therapy
• Comorbidity
• Biological Factors/therapeutic use

• Inflammation
• Nonalcoholic fatty liver disease
• Nonalcoholic steatohepatitis
• Treatment
• Tumor necrosis factor-α

• Humans
• Non-alcoholic Fatty Liver Disease/metabolism
• Tumor Necrosis Factor-alpha/therapeutic use
• Tumor Necrosis Factor Inhibitors/therapeutic use
• Cytokines

• Aristotle University of Thessaloniki

• Adult
• Humans
• Non-alcoholic Fatty Liver Disease/complications
• Prospective Studies
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/drug therapy
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/drug therapy
• Steroids

• Biologics
• inflammatory bowel diseases
• nonalcoholic fatty liver disease

Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders. They can occur at any moment in the course of the disease or associated with the treatment. The prevalence of liver dysfunction can reach up to 50% in different studies. Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD, while primary sclerosing cholangitis is the most specific. Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists. The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD, associated diseases or to the therapies used.

• Extraintestinal manifestations
• Inflammatory bowel disease
• Sclerosing primary cholangitis
• Hepatic steatosis
• Liver toxicity

• adalimumab
• cirrhosis
• etanercept
• rheumatoid arthritis
• tumor necrosis factor-α inhibitors

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases (IBD), both in Crohn’s disease and ulcerative colitis (UC), and therefore represent a diagnostic challenge. Immune-mediated conditions include primary sclerosing cholangitis (PSC) as the main form, variant forms of PSC (namely small-duct PSC, PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis) and granulomatous hepatitis. PSC is by far the most common, presenting in up to 8% of IBD patients, more frequently in UC. Several genetic foci have been identified, but environmental factors are preponderant on disease pathogenesis. The course of the two diseases is typically independent. PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies. Risk of cholangiocarcinoma is significantly increased in PSC, as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis. No disease-modifying drugs are approved to date. Thus, PSC management is directed against symptoms and complications and includes medical therapies for pruritus, endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease. Other non-immune-mediated hepatobiliary disorders are gallstone disease, whose incidence is higher in IBD and reported in up to one third of IBD patients, non-alcoholic fatty liver disease, pyogenic liver abscess and portal vein thrombosis. Drug-induced liver injury (DILI) is an important issue in IBD, since most IBD therapies may cause liver toxicity; however, the incidence of serious adverse events is low. Thiopurines and methotrexate are the most associated with DILI, while the risk related to anti-tumor necrosis factor-α and anti-integrins is low. Data on hepatotoxicity of newer drugs approved for IBD, like anti-interleukin 12/23 and tofacitinib, are still scarce, but the evidence from other rheumatic diseases is reassuring. Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD, and adequate screening and vaccination is warranted. On the other hand, hepatitis C reactivation does not seem to be a real risk, and hepatitis C antiviral treatment does not influence IBD natural history. The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis, but it is of paramount importance to make a quick and accurate diagnosis, as it may influence the therapeutic management.

• Inflammatory bowel diseases
• Hepatobiliary disorders
• Primary sclerosing cholangitis
• Drug-induced liver injury
• Biological drugs
• Viral hepatitis

Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common cause of liver disease. Its prevalence is increasing in parallel with the obesity and type 2 diabetes mellitus (DM2) epidemics in developed countries. Several recent studies have suggested that NAFLD may be the hepatic manifestation of a systemic inflammatory metabolic disease that also affects other organs, such as intestine, lungs, skin and vascular endothelium. It appears that local and systemic proinflammatory/anti-inflammatory cytokine imbalance, together with insulin resistance and changes in the intestinal microbiota, are pathogenic mechanisms shared by NAFLD and other comorbidities. NAFLD is more common in patients with extrahepatic diseases such as inflammatory bowel disease (IBD), obstructive syndrome apnea (OSA) and psoriasis than in the general population. Furthermore, there is evidence that this association has a negative impact on the severity of liver lesions. Specific risk characteristics for NAFLD have been identified in populations with IBD (i.e. age, obesity, DM2, previous bowel surgery, IBD evolution time, methotrexate treatment), OSA (i.e. obesity, DM2, OSA severity, increased transaminases) and psoriasis (i.e. age, metabolic factors, severe psoriasis, arthropathy, elevated transaminases, methotrexate treatment). These specific phenotypes might be used by gastroenterologists, pneumologists and dermatologists to create screening algorithms for NAFLD. Such algorithms should include non-invasive markers of fibrosis used in NAFLD to select subjects for referral to the hepatologist. Prospective, controlled studies in NAFLD patients with extrahepatic comorbidities are required to demonstrate a causal relationship and also that appropriate multidisciplinary management improves these patients’ prognosis and survival.

• Non-alcoholic fatty liver disease
• Liver fibrosis
• Psoriasis
• Obstructive sleep apnea
• Metabolic syndrome
• Inflammatory bowel disease

• Diabetes Mellitus, Type 2
• Humans
• Intestines
• Lung
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/therapy
• Prospective Studies
• Psoriasis
• Risk Factors

• Crohn's disease
• TNF-alpha
• microbiota
• steatosis

• Crohn’s disease
• Inflammatory bowel disease
• NAFLD fibrosis score
• Nonalcoholic fatty liver disease
• Ulcerative colitis

• Biomarkers/blood
• Disease Progression
• Female
• Humans
• Inflammatory Bowel Diseases/blood
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/epidemiology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/etiology
• Liver Function Tests/methods
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/epidemiology
• Prevalence
• Retrospective Studies
• Risk Assessment/methods
• Risk Factors
• Severity of Illness Index
• United States/epidemiology

• T32 DK067872 NIDDK NIH HHS

There has been a worldwide increase in the reported incidence of inflammatory bowel disease (IBD) in children over the past 2-3 decades. The hepatobiliary (HB) manifestations of IBD have been well-studied in children in industrialized and developed countries but are infrequently reported in low- and middle-income countries (LMIC) such as Egypt.

To determine the prevalence of the HB manifestations in a cohort of Egyptian children with IBD.

This cross-sectional observational study was carried out over a period of 6 mo (between June 2013 to December 2013) at the Paediatric Hepatology and Gastroenterology Units of Cairo University Children's Hospital, which is the largest paediatric tertiary care centre in the country.

The study included 48 patients with confirmed IBD based upon clinical, laboratory, endoscopic and histopathological features, 29 (60.4%) were male. Twenty-four patients (50%) had ulcerative colitis (UC), 11 (22.9%) had Crohn's disease (CD) and 13 (27.1%) had unclassified-IBD (IBD-U), which was formerly known as indeterminate colitis. The mean age of the patients at the time of presentation was 8.14 (± SD 4.02) years and the mean age at the time of study enrolment was 10.16 (± SD 4.19) years. All patients were screened for HB manifestations by physical examination, liver function tests, imaging and liver biopsy when indicated. HB disorders were confirmed in 13 patients (27.1%). Transaminases were elevated in 3 patients (6.3%). Two patients (4.2%) had elevated biliary enzymes (one was diagnosed as primary sclerosing cholangitis (PSC) and the other was diagnosed with PSC/autoimmune hepatitis overlap syndrome and the third patient had hepatitis C virus infection. Ten patients (20.8%) had bright echogenic liver on ultrasound suggesting fatty infiltration as a sequel of malnutrition or medication toxicity.

The commonest HB disorders in Egyptian children with IBD were abnormal liver function tests, fatty infiltration and PSC. These HB manifestations in paediatric patients in LMIC may be relatively more common than in industrialized countries. Therefore, IBD patients in LMIC should be meticulously screened for liver disease to allow prompt diagnosis and management.

• Children
• Crohn's disease
• Egypt
• Elevated liver enzymes
• Hepatobiliary
• Inflammatory bowel disease
• Ulcerative colitis

• Fatty liver
• Nonalcoholic fatty liver disease
• Nonalcoholic steatohepatitis

Elevated tumour necrosis factor (TNF)-α has been implicated in the progression of liver fibrosis and pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aim to investigate the impact of anti-TNF-α agents on the development of cirrhosis and NAFLD.

This retrospective cohort study used a US claims database between 1 January 2010 and 31 December 2016. We identified adult patients with ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis or rheumatoid arthritis. Anti-TNF-α agents of interest included adalimumab, certolizumab, etanercept, golimumab and infliximab. The primary composite outcome was the development of new-onset cirrhosis, NAFLD or non-alcoholic steatohepatitis (NASH). The secondary outcomes were the development of (1) cirrhosis and (2) NAFLD or NASH. Propensity score for anti-TNF-α agent use was generated by logistic regression. Cox proportional hazard models adjusting for the propensity score were used with regard to time-varying anti-TNF-α agent exposure.

This study included 226 555 incident patients with immune-related diseases. During the median 1.5 years follow-up, there was an increased hazard with anti-TNF-α agent use in regard to liver outcomes (composite outcome HR: 1.47, 95% CI 1.27 to 1.70; cirrhosis HR 1.47, 95% CI 0.96 to 2.23; NAFLD or NASH HR 1.53, 95% CI 1.32 to 1.77). The composite outcome hazard was increased for each immune-related disease (HR 1.25–1.90).

In the short term, we did not observe a beneficial effect of anti-TNF-α agent use for development of cirrhosis, NAFLD or NASH in patients with immune-related diseases.

• IBD
• TNF-alpha
• liver cirrhosis
• nonalcoholic steatohepatitis

• Crohn’s disease
• prevalence
• risk factor
• steatohepatitis
• ulcerative colitis

Non-alcoholic fatty liver disease (NAFLD) is common in patients with inflammatory bowel disease (IBD). This study evaluated the prevalence of NAFLD and the associated risk factors among IBD patients who received anti-tumor necrosis factor (TNF) therapy.

Adult IBD patients receiving anti-TNF therapy (infliximab, adalimumab, certolizumab, golimumab) were enrolled. Hepatic steatosis was assessed by abdominal ultrasound. Patients with a history of excessive alcohol or recent steroid use were excluded. Univariate and multivariate analysis were performed.

Eighty patients, 55% male, mean age 42±15 years, were enrolled. The sonographic prevalence of NAFLD was 54% (43/80), significantly higher than the general prevalence in the US adult population (30%) (P<0.0001). NAFLD patients had a significantly higher proportion of males, as well as greater body weight and body mass index, compared to non-NAFLD. The Crohns disease activity index (CDAI) was significantly higher among patients with NAFLD. Multivariate analysis demonstrated that a higher CDAI was independently associated with NAFLD, with an odds ratio of 1.6 (95% confidence interval 1.05-2.44; P=0.03).

The presence of IBD is strongly associated with NAFLD. We identified a high prevalence of NAFLD among IBD patients receiving anti-TNF. CDAI was independently associated with hepatic steatosis. Further studies are still needed to evaluate the pathophysiology of NAFLD development and disease progression among IBD populations.

• Hepatic steatosis
• anti-tumor necrosis factor
• inflammatory bowel disease
• non-alcoholic fatty liver disease

Background and Aim: Most studies focused on the benefits of weight loss on hepatic steatosis and no studies have been specifically designed to assess the role of weight gain on the development of liver steatosis in patients affected by inflammatory bowel diseases. The aim of this study was to analyse the relation between weight change over time and liver steatosis in patients with inflammatory bowel diseases. Methods: We retrospectively evaluated a population of 89 ambulatory patients in clinical remission or affected by mild disease, as determined from disease activity indices, with at least one follow-up visit. Transient elastography was used to quantify liver steatosis. Results: A total of 49 individuals (55%) were overweight/obese at baseline. A significant difference in weight change was found between participants that improved, were stable and worsened, over a mean follow-up of four years. (−1.0 kg ± 4; 2.5 kg ± 6; and 5.4 kg ± 5; respectively, p = 0.009). We found a greater probability of worsening in the hepatic fat content in individuals who gained more than 6% of body weight than in those gaining less than this value (log–rank (Mantel–Cox) χ² test = 9.85; df = 1; p = 0.002). Conclusions: A body weight gain of 6% increases the probability of deterioration in liver steatosis over a period of four years in patients with inflammatory bowel diseases. Weight gain prevention with lifestyle interventions may be the cornerstone treatment of these patients.

• hepatic steatosis
• inflammatory bowel diseases
• transient elastography
• weight gain

To estimate the risk of end-stage renal disease (ESRD) in patients with inflammatory bowel disease (IBD).

From January 2010 to December 2013, patients with Crohn’s disease (CD) and ulcerative colitis (UC) were identified, based on both the International Classification of Diseases, 10^th revision (ICD-10) and the rare, intractable disease registration program codes from the National Health Insurance (NHI) database in South Korea. We compared 38812 patients with IBD to age- and sex-matched non-IBD controls with a ratio of 1:3. Patients newly diagnosed with ESRD were identified with the ICD-10 code.

During a mean follow-up of 4.9 years, ESRD was detected in 79 (0.2%) patients with IBD and 166 (0.1%) controls. The incidence of ESRD in patients with IBD was 0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio (HR) = 3.03; 95% confidence interval (CI): 1.77-5.20; P < 0.001]. The incidences (per 1000 person-years) of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively (adjusted HR = 6.33; 95%CI: 2.75-14.56; P < 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups (0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01; 95%CI: 0.90-4.51; P = 0.089).

The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.

• Claims data
• Inflammatory bowel disease
• Crohn’s disease
• End-stage renal disease
• Ulcerative colitis

• Adolescent
• Adult
• Case-Control Studies
• Colitis, Ulcerative/epidemiology
• Comorbidity
• Crohn Disease/epidemiology
• Female
• Follow-Up Studies
• Humans
• Incidence
• Kidney Failure, Chronic/epidemiology
• Male
• Middle Aged
• Republic of Korea/epidemiology
• Retrospective Studies
• Risk Assessment
• Risk Factors
• Young Adult